Molecular Genetic Analysis of One Sudden Unexplained Death in the Young by Whole Exome Sequencing / 法医学杂志

ABSTRACT

Objective To find the mutation of disease-causing genes of sudden unexplained death syn-drome (SU D S ) in the young by whole exome sequencing in one case. Methods O ne SU D S case was found no obvious fatal pathological changes after conventional autopsy and pathological examination. The whole exome sequencing was performed with the Ion Torrent PGMTM Systemwith hg19 as reference se-quence for sequencing data. The functions of mutations were analyzed by PhyloP, PolyPhen2 and SIFT. A three-step bioinformatics filtering procedure was carried out to identify possible significative single nu-cleotide variation (SN V ), which was missense mutation with allele frequency <1% of myocardial cell. Results Four rare suspicious pathogenic SN V were identified. C ombined with the analysis of convention-al autopsy and pathological examination, the mutation MYOM 2 (8_2054058_G/A ) was assessed as high-risk deleterious mutation by PolyPhen2 and SIFT, respectively. Conclusion Based on the second genera-tion sequencing technology, analysis of whole exome sequencing can be a newmethod for the death cause investigation of SU D S. The gene MYOM2 is a newcandidate SU D S pathogenic gene for mecha-nismresearch.